A number of naturally occurring antimicrobial systems rely upon the ability of certain oxidizing agents to disrupt metabolic processes of bacteria, fungi and viruses. Examples of such oxidizing agents include hypothiocyanite (OSCN-/ HOSCN), hypochlorite (OCl- .backslash.HOCl), and hypoiodite (OI-.backslash.HOI). These agents are known to inhibit glycolysis, penetrate prokaryotic cell walls, and generally disrupt a wide variety of processes crucial to the survival of lower organisms at concentrations greater than or equal to about 100 micromoles per liter. The oxidizing agents are formed from the detoxification of hydrogen peroxide by mammalian peroxidase systems, such as those found in saliva, cervical fluid, lachrymal fluid, and leukocytes. Examples of such peroxidase system enzymes are myeloperoxidase, lactoperoxidase, and salivary peroxidase.
Attempts to exploit these natural antimicrobial systems have been directed to both the oral care field and the gastrointestinal tract. U.S. Pat No. 4,150,113 and U.S. Pat. No. 4,178,362 (Hoogendorn, et al.) describe dentifrice compositions containing glucose oxidase that react with plaque and salivary glucose to produce low levels of hydrogen peroxide. Hydrogen peroxide production by such systems is, however, highly irregular due to the non-uniform distribution and unpredictable availability of substrate, namely glucose, in the oral cavity.
U.S. Pat No. 4,269,822, U.S. Pat No. 4,564,519 and U.S. Pat. No. 4,578,265 (Pellico, et al.) further describe dentifrice compositions containing an oxidoreductase enzyme and its specific substrate in an aqueous solution for the purpose of producing hydrogen peroxide or other antimicrobial oxidizing compounds such as hypothiocyanite ion. A more predictable amount of hydrogen peroxide (and subsequently hypothiocyanite ions) is produced by the compositions of Pellico et al., compared with those of the Hoogendorn references. The differences between the two compositions reflect the availability of glucose in the oral cavity as substrate for glucose oxidase.
There are, however, a number of disadvantages associated with the compositions of Pellico et al. These include: the limited rate of enzymatically-produced hydrogen peroxide that in turn produces the hypothiocyanite ion. The short duration of oral contact time, namely during toothbrushing, means that insufficient amounts of hypothiocyanite is available to effectively eliminate microbes in the oral cavity. In addition, the references utilize glucose oxidase as the oxidoreductase enzyme that in turn relies upon the availability of a sufficient concentration of glucose in solution to produce hydrogen peroxide. However, the glucose itself is a microbial substrate and is potentially cariogenic when present in an oral care product.
U.S. Pat No. 4,564,519 describes a chewable dentifrice, such as a chewing gum or lozenge, which contains a dual enzyme system for producing hypothiocyanite ions upon being chewed or otherwise activated by the moisture in saliva. Such compositions suffer from similar drawbacks to those mentioned immediately above namely a slow rate of enzymatically-produced hydrogen peroxidase as well as a reliance on a cariogenic compound.
Other solid or chewable compositions capable of producing hydrogen peroxide or other oxidizing agents upon activation with moisture are taught in U.S. Pat. No. 4,320,116, U.S. Pat. No. 4,726,948, and U.S. Pat. No. 4,929,466. These compositions are foodstuffs intended for consumption by livestock in order to limit the growth of harmful bacterial within the animal's gastrointestinal tract. These references describe the use of various enzymatic and non-enzymatic sources for hydrogen peroxide, where the enzymatic sources are glucose oxidase/glucose and the non-enzymatic sources are sodium perborate, sodium percarbonate, and calcium peroxide. However, it is known that sodium percarbonate and potassium percarbonate have extremely alkaline pH and are thus of little use in activating the peroxidase enzymes until exposed to the acidic environment within the gastrointestinal tract. Thus, the foodstuff compositions described in the reference cannot be used as a therapeutic or otherwise peroxidase-activating effect in the oral cavity.
It would thus be advantageous to provide substantially non-cariogenic compositions capable of rapidly producing hydrogen peroxide in conditions that are suitable for peroxidase enzyme activation in the oral cavity.
It would also be advantageous to provide compositions capable of rapidly producing antimicrobial hypohalite ions within the limited contact time available in most oral hygiene procedures.
It would also be advantageous to provide compositions capable of rapidly producing antimicrobial hypohalite ions upon contact with saliva within the limited contact time available in most oral hygiene procedures.